This proposal describes a plan to study frontotemporal lobar degeneration (FTLD) using the infrastructure established by the Alzheimer's Disease Neuroimaging Initiative (ADNI). FTLD is a common cause of dementia, especially in patients under the age of 65, with large economic and social costs. Over the next few years, potential therapeutic agents for FTLD will likely emerge and require clinical testing. In preparation for these clinical trials, it is important to establish precise, reliable and cost-effective markers for disease progression, to maximize the power of treatment trials to detect disease modifying effects. In the proposed study, 120 patients with FTLD and 120 age-matched controls will be studied with MRI, FDG-PET, and blood, urine and CSF biomarkers over the course of one year to determine the best regions and best methods for following the progression of FTLD. All patients will also undergo PIB-PET scanning, which identifies beta-amyloid plaques associated with Alzheimer's disease. The specific aims of the study are: 1) To identify the regions where FTLD shows greatest longitudinal changes in glucose metabolism, cerebral perfusion, and gray matter volume with the lowest variance, 2) To identify regions where FTLD shows greatest longitudinal changes with lowest variance in white matter tract integrity, 3) To contrast the performance of FDG-PET, ASL perfusion, gray matter volume and white matter tract integrity to detect longitudinal changes in FTLD, 4) To establish the clinical correlates of longitudinal changes in glucose metabolism, perfusion, gray matter volume and white matter integrity in FTLD, 5) To quantify the changes in CSF tau and A-beta1-42 levels and tau/abeta ratios over time in FTLD, and 6) To define the metabolic, structural imaging and CSF biomarker features predicting increased PIB retention with a clinical diagnosis of FTLD. Should these aims be achieved, the proposed study would provide firm data about which regions are the most sensitive indicators for following the course of disease in FTLD, and whether PET is significantly better than MRI for this purpose or visa-versa. The data would also provide estimates from which power could be calculated for clinical studies. All the data will eventually be available in a publicly accessible database for use by other researchers. PUBLIC HEALTH RELEVANCE: The frontotemporal lobar degeneration (FTLD) neuroimaging initiative will provide information on how to use brain images to follow the course of FTLD over time, and what techniques are best for this purpose. This information will be valuable to researchers planning trials of new medications for FTLD, so they can use brain imaging to help decide which drugs show the most promise for treating the disease.